In this report, we compared the adaptive immune responses following halothane treatment of normal female Balb/cJ mice to Balb/cJ mice depleted of regulatory T cells. Mice depleted of regulatory T cells had significantly higher serum levels of anti-TFA-protein antibodies and elevated T cell proliferation when treated in culture with TFA-protein adducts as compared to normal Balb/cJ mice. Moreover, there was a significant infiltration of TGF-beta-producing T regulatory cells into the liver of normal Balb/cJ mice following halothane treatment. These results suggest that T regulatory cells may have an important inhibitory effect on the adaptive immune system reaction against protein adducts of drugs released from damaged hepatocytes and immunopathology against the liver. Conclusion: These preliminary findings warrant further studies into the role of regulatory T cells in the mechanisms and susceptibility to DILD.